Enhanced bioprocess control to advance the manufacture of mesenchymal stromal cell-derived extracellular vesicles in stirred-tank bioreactors

Detalhes bibliográficos
Autor(a) principal: Costa, Marta H.G.
Data de Publicação: 2023
Outros Autores: Costa, Margarida S., Painho, Beatriz, Sousa, Carolina D., Carrondo, Inês, Oltra, Enrique, Pelacho, Beatriz, Prosper, Felipe, Isidro, Inês A., Alves, Paula, Serra, Margarida
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/158648
Resumo: Funding Information: The authors acknowledge A.L. Sousa and E.M. Tranfield from the Electron Microscopy Facility at the IGC for the transmission electron microscopy work. Rafael Fernandes, from Endress-Hauser, is also acknowledged for his support during the Raman spectroscopy studies. This work was supported by EU Interreg Sudoe—funded project CardioPatch (SOE4/P1/E1063), iNOVA4Health—UIDB/04462/2020 and UIDP/04462/2020, a program financially supported by FCT/Ministério da Ciência, Tecnologia e Ensino Superior, through national funds. The Associate Laboratory LS4FUTURE (LA/P/0087/2020) is also acknowledged. Funding Information: The authors acknowledge A.L. Sousa and E.M. Tranfield from the Electron Microscopy Facility at the IGC for the transmission electron microscopy work. Rafael Fernandes, from Endress‐Hauser, is also acknowledged for his support during the Raman spectroscopy studies. This work was supported by EU Interreg Sudoe—funded project CardioPatch (SOE4/P1/E1063), iNOVA4Health—UIDB/04462/2020 and UIDP/04462/2020, a program financially supported by FCT/Ministério da Ciência, Tecnologia e Ensino Superior, through national funds. The Associate Laboratory LS4FUTURE (LA/P/0087/2020) is also acknowledged. Publisher Copyright: © 2023 iBET - Instituto de Biologia Experimental e Tecnológica. Biotechnology and Bioengineering published by Wiley Periodicals LLC.
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spelling Enhanced bioprocess control to advance the manufacture of mesenchymal stromal cell-derived extracellular vesicles in stirred-tank bioreactorsbioprocess analyticsextracellular vesicles (EVs)mesenchymal stem/stromal cells (MSCs)metabolic preconditioningRaman spectroscopystirred-tank bioreactorsBiotechnologyBioengineeringApplied Microbiology and BiotechnologyFunding Information: The authors acknowledge A.L. Sousa and E.M. Tranfield from the Electron Microscopy Facility at the IGC for the transmission electron microscopy work. Rafael Fernandes, from Endress-Hauser, is also acknowledged for his support during the Raman spectroscopy studies. This work was supported by EU Interreg Sudoe—funded project CardioPatch (SOE4/P1/E1063), iNOVA4Health—UIDB/04462/2020 and UIDP/04462/2020, a program financially supported by FCT/Ministério da Ciência, Tecnologia e Ensino Superior, through national funds. The Associate Laboratory LS4FUTURE (LA/P/0087/2020) is also acknowledged. Funding Information: The authors acknowledge A.L. Sousa and E.M. Tranfield from the Electron Microscopy Facility at the IGC for the transmission electron microscopy work. Rafael Fernandes, from Endress‐Hauser, is also acknowledged for his support during the Raman spectroscopy studies. This work was supported by EU Interreg Sudoe—funded project CardioPatch (SOE4/P1/E1063), iNOVA4Health—UIDB/04462/2020 and UIDP/04462/2020, a program financially supported by FCT/Ministério da Ciência, Tecnologia e Ensino Superior, through national funds. The Associate Laboratory LS4FUTURE (LA/P/0087/2020) is also acknowledged. Publisher Copyright: © 2023 iBET - Instituto de Biologia Experimental e Tecnológica. Biotechnology and Bioengineering published by Wiley Periodicals LLC.Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) act as signaling mediators of cellular responses. However, despite representing a promising alternative to cell-based therapies, clinical translation of EVs is currently limited by their lack of scalability and standardized bioprocessing. Herein, we integrated scalable downstream processing protocols with standardized expansion of large numbers of viable cells in stirred-tank bioreactors to improve EV production. Higher EV yields were linked to EV isolation by tangential flow filtration followed by size exclusion chromatography, rendering 5 times higher number of EVs comparatively to density gradient ultracentrifugation protocols. Additionally, when compared to static culture, EV manufacture in bioreactors resulted in 2.2 higher yields. Highlighting the role of operating under optimal cell culture conditions to maximize the number of EVs secreted per cell, MSCs cultured at lower glucose concentration favored EV secretion. While offline measurements of metabolites concentration can be performed, in this work, Raman spectroscopy was also applied to continuously track glucose levels in stirred-tank bioreactors, contributing to streamline the selection of optimal EV collection timepoints. Importantly, MSC-derived EVs retained their quality attributes and were able to stimulate angiogenesis in vitro, therefore highlighting their promising therapeutic potential.Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNCosta, Marta H.G.Costa, Margarida S.Painho, BeatrizSousa, Carolina D.Carrondo, InêsOltra, EnriquePelacho, BeatrizProsper, FelipeIsidro, Inês A.Alves, PaulaSerra, Margarida2023-10-03T22:18:48Z2023-092023-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article17application/pdfhttp://hdl.handle.net/10362/158648eng0006-3592PURE: 72616213https://doi.org/10.1002/bit.28378info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:41:11Zoai:run.unl.pt:10362/158648Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:57:14.892344Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Enhanced bioprocess control to advance the manufacture of mesenchymal stromal cell-derived extracellular vesicles in stirred-tank bioreactors
title Enhanced bioprocess control to advance the manufacture of mesenchymal stromal cell-derived extracellular vesicles in stirred-tank bioreactors
spellingShingle Enhanced bioprocess control to advance the manufacture of mesenchymal stromal cell-derived extracellular vesicles in stirred-tank bioreactors
Costa, Marta H.G.
bioprocess analytics
extracellular vesicles (EVs)
mesenchymal stem/stromal cells (MSCs)
metabolic preconditioning
Raman spectroscopy
stirred-tank bioreactors
Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
title_short Enhanced bioprocess control to advance the manufacture of mesenchymal stromal cell-derived extracellular vesicles in stirred-tank bioreactors
title_full Enhanced bioprocess control to advance the manufacture of mesenchymal stromal cell-derived extracellular vesicles in stirred-tank bioreactors
title_fullStr Enhanced bioprocess control to advance the manufacture of mesenchymal stromal cell-derived extracellular vesicles in stirred-tank bioreactors
title_full_unstemmed Enhanced bioprocess control to advance the manufacture of mesenchymal stromal cell-derived extracellular vesicles in stirred-tank bioreactors
title_sort Enhanced bioprocess control to advance the manufacture of mesenchymal stromal cell-derived extracellular vesicles in stirred-tank bioreactors
author Costa, Marta H.G.
author_facet Costa, Marta H.G.
Costa, Margarida S.
Painho, Beatriz
Sousa, Carolina D.
Carrondo, Inês
Oltra, Enrique
Pelacho, Beatriz
Prosper, Felipe
Isidro, Inês A.
Alves, Paula
Serra, Margarida
author_role author
author2 Costa, Margarida S.
Painho, Beatriz
Sousa, Carolina D.
Carrondo, Inês
Oltra, Enrique
Pelacho, Beatriz
Prosper, Felipe
Isidro, Inês A.
Alves, Paula
Serra, Margarida
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
RUN
dc.contributor.author.fl_str_mv Costa, Marta H.G.
Costa, Margarida S.
Painho, Beatriz
Sousa, Carolina D.
Carrondo, Inês
Oltra, Enrique
Pelacho, Beatriz
Prosper, Felipe
Isidro, Inês A.
Alves, Paula
Serra, Margarida
dc.subject.por.fl_str_mv bioprocess analytics
extracellular vesicles (EVs)
mesenchymal stem/stromal cells (MSCs)
metabolic preconditioning
Raman spectroscopy
stirred-tank bioreactors
Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
topic bioprocess analytics
extracellular vesicles (EVs)
mesenchymal stem/stromal cells (MSCs)
metabolic preconditioning
Raman spectroscopy
stirred-tank bioreactors
Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
description Funding Information: The authors acknowledge A.L. Sousa and E.M. Tranfield from the Electron Microscopy Facility at the IGC for the transmission electron microscopy work. Rafael Fernandes, from Endress-Hauser, is also acknowledged for his support during the Raman spectroscopy studies. This work was supported by EU Interreg Sudoe—funded project CardioPatch (SOE4/P1/E1063), iNOVA4Health—UIDB/04462/2020 and UIDP/04462/2020, a program financially supported by FCT/Ministério da Ciência, Tecnologia e Ensino Superior, through national funds. The Associate Laboratory LS4FUTURE (LA/P/0087/2020) is also acknowledged. Funding Information: The authors acknowledge A.L. Sousa and E.M. Tranfield from the Electron Microscopy Facility at the IGC for the transmission electron microscopy work. Rafael Fernandes, from Endress‐Hauser, is also acknowledged for his support during the Raman spectroscopy studies. This work was supported by EU Interreg Sudoe—funded project CardioPatch (SOE4/P1/E1063), iNOVA4Health—UIDB/04462/2020 and UIDP/04462/2020, a program financially supported by FCT/Ministério da Ciência, Tecnologia e Ensino Superior, through national funds. The Associate Laboratory LS4FUTURE (LA/P/0087/2020) is also acknowledged. Publisher Copyright: © 2023 iBET - Instituto de Biologia Experimental e Tecnológica. Biotechnology and Bioengineering published by Wiley Periodicals LLC.
publishDate 2023
dc.date.none.fl_str_mv 2023-10-03T22:18:48Z
2023-09
2023-09-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/158648
url http://hdl.handle.net/10362/158648
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0006-3592
PURE: 72616213
https://doi.org/10.1002/bit.28378
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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